The Hepatitis B Research Network (HBRN) was established in 2008 as a consortium of clinical and translational investigators studying novel aspects of hepatitis B disease. The focus of the HBRN has been to further elucidate the natural history of chronic hepatitis B in the United States and to conduct clinical trials comparing monotherapy versus combination therapy in immuneactive (IA) and immunetolerant (IT) populations. Numerous epidemiological studies utilizing the baseline data from the Adult Cohort Study have been implemented and several have been published or submitted for publication. Similarly, ancillary studies that will further our understanding of HBV pathogenesis, utilizing the robust clinical data linked with biospecimens, have been initiated. This renewal application will focus on continuing the extraordinary efforts of the HBRN, detail the integral role of The North Carolina Hepatitis B Research Consortium in this endeavor, and propose novel translational studies that will contribute to understanding HBV pathogenesis.